69MO - Organ-specific performance of a multi-analyte, multi-cancer early detection (MCED) blood test in a prospectively-collected cohort

Background

A multi-analyte blood test has the potential to detect a broad range of cancer types and stages. We previously trained and independently assessed the performance of four biomarker classes for cancer detection in a retrospective, case-control study (Annals of Oncology, 2022; 33(7Supp): S575). The aim of this study was to assess organ-specific performance of two of the four biomarker classes (methylation and protein) using samples from a large, multi-center, prospectively collected study.

Methods

This study included 6,190 samples (1,383 cancer and 4,807 non-cancer) representing all stages of 21 cancer types divided approximately equally between a training cohort included (n=3,027) and a test set (n=3,163). Sensitivity of a combined DNA methylation and protein biomarker classifier was determined at a combined specificity of ≥98.5%. For detailed methods see Cancer Res, 2024; 84(7Supp): LB100.

Results

The observed overall test set sensitivity was 50.9% and 98.5% specificity, with sensitivities ranging from 11.8% (prostate) to 80.0% (liver & bile duct). Sensitivities were 15.4% and 38.0% for Stage I and Stage II cancers, respectively. Sensitivity for cancers without recommended screening for average risk populations was 54.8%, and 63.7% for the six most lethal cancers (pancreas, esophagus, liver & bile duct, lung & bronchus, stomach, and ovary). Performance by organ type is shown in the table. Table: 69MO

Performance by organ type

Conclusions

Methylation and protein biomarkers exhibited robust performance across all cancer organ types, including those without standard of care screening options and aggressive cancers with poor 5-year survival. These results demonstrate the potential clinical utility of a multi-biomarker class approach for the detection of several cancer types.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Exact Sciences Corporation.

Funding

Exact Sciences Corporation.

Disclosure

C. Douville: Financial Interests, Personal, Advisory Role: Exact Sciences Corporation; Financial Interests, Personal, Royalties: Johns Hopkins University. V. Gainullin, K. Arvai, M. Gray, M. Kumar, M. Manesse, X. Chen, G. Cerqueira, A. Mazloom, F. Diehl: Financial Interests, Personal, Full or part-time Employment: Exact Sciences Corporation; Financial Interests, Personal, Stocks/Shares: Exact Sciences Corporation. P. Uren: Financial Interests, Personal, Full or part-time Employment: Exact Sciences Corporation; Financial Interests, Personal, Stocks/Shares: Exact Sciences Corporation; Financial Interests, Personal, Stocks or ownership: Biora Biosciences. G. Silvestri: Financial Interests, Personal, Advisory Board: Candel Therapeutics; Financial Interests, Personal, Other, consulting fees: Freenome, Biodesix; Financial Interests, Institutional, Research Funding: Nucleix, Inc, Biodesix, Delfi Diagnostics, Freenome. R. Given: Financial Interests, Personal, Speaker’s Bureau: Bayer, Janssen, Myovant. J. Garces: Financial Interests, Personal, Full or part-time Employment: Exact Sciences Corporation; Financial Interests, Personal, Stocks/Shares: Exact Sciences Corporation; Financial Interests, Personal, Officer, Chief Scientific Officer: Exact Sciences Corporation. T.M. Beer: Financial Interests, Personal, Full or part-time Employment: Exact Sciences Corporation; Financial Interests, Personal, Stocks/Shares: Exact Sciences Corporation, Osteologic, Salarius Pharmaceuticals, Osheru; Financial Interests, Personal, Advisory Role: Arvinas, AstraZeneca, GSK, Sanofi; Financial Interests, Institutional, Research Funding: Alliance Foundation Trials, Astellas Pharma, Freenome, GRAIL, Bayer. All other authors have declared no conflicts of interest.